Objective: Because our previous studies in several vascular preparations suggest that posthypoxic reoxygenation elicits tone responses by generation of hydrogen peroxide we compared the actions of reoxygenation and hydrogen peroxide on isolated human placental arteries and veins. Study Design: Endothelium-intact and denuded arteries and veins (1 to 2 mm diameter, from normal term deliveries), incubated under 95% oxygen/5% carbon dioxide or 5% oxygen/5% carbon dioxide (balance nitrogen) and precontracted with 1 to 10 nmol/L U46619, were exposed to hypoxia (95% nitrogen/5% carbon dioxide, Po2 8 to 10 torr) followed by reoxygenation and to 1 to 100 µmol/L hydrogen peroxide in the presence and absence of the inhibitor of prostaglandin biosynthesis, 10 µ-mol/L indomethacin. Results: In both arteries and veins posthypoxic reoxygenation or exposure to hydrogen peroxide produced vascular contraction that was eliminated or reversed to a modest relaxation by indomethacin, consistent with mediation by prostaglandins. Hypoxia after incubation with 5% oxygen, but not 95% oxygen, caused a modest prostaglandin-independent relaxation. Removal of the endothelium did not alter any of these responses. Conclusion: Placental arteries and veins show a similar prostaglandin-mediated contraction to hydrogen peroxide and posthypoxic reoxygenation, consistent with a possible involvement of hydrogen peroxide in the response to reoxygenation.